Olfactory perception is mediated in mammals by two anatomically and functionally distinct sensory organs: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). While the MOE mediates detection of a wide variety of odorants, the VNO is responsible for recognition of pheromones. These are chemical signals that provide information about gender, dominance, or reproductive status. The recent isolation of a gene family encoding putative pheromone receptors provides a basis to study the molecular biology of pheromone perception. To date, however, there is no evidence that these proteins are pheromone receptors. Here, genetic proof is sought for the hypothesis that these genes encode molecules involved in pheromone perception. The applicant will attempt to identify a VNO receptor gene that is differentially expressed in the male or female, introduce a knock-out mutation in that gene, and assess the phenotype of the knock-out mice. The applicant will determine the ends of the cluster of VNO receptor genes, delete the whole gene family by chromosome engineering techniques, and assess the phenotype of the mutant mice.